Various methods for intraocular drug delivery are known. For example, drugs may be administered topically by introducing eye drops into the eye. Generally, however, topical administration is only effective for treating conditions on the surface of the eye and to a lesser extent the anterior segment of the eye; it is difficult to deliver drugs in therapeutic concentrations beyond the cornea.
Intraocular injections have also been used to deliver drugs to the inside of the eye at therapeutic concentrations. However, such invasive methods of drug delivery require great technical skill and are extremely unpleasant for the patient. There is also the risk of infection, inflammation, hypotony, choroidal detachment, retinal detachment and haemorrhage with their consequent complications (that may in themselves lead to blindness).
To avoid injecting drugs directly into the eye, drugs may be administered by enteral (for example orally) or other parenteral routes (for example intravenously) and these may reach the eye via the circulation. Generally, however, these drugs have to be administered at high concentrations, since the active compound may be diluted by intravascular and extravascular fluids. This gives rise to a risk of toxicity to other organ systems and tissues. If lower concentrations are used to avoid toxicity and other side effects there is more risk of treatment failure, for example, due to the inactivation and/or excretion of the active compound by the liver and kidneys before it reaches the eye, particularly if the compound cycles repeatedly through these organs.
WO 01/51087 describes a method for treating neovascular diseases of the eye using photodynamic therapy (PDT). In PDT, a photosensitive compound is administered to the patient systemically or topically. The photosensitive compound has a characteristic light absorption spectrum and, when exposed to light within that waveband, produces reactive species, such as singlet oxygen atoms, which damage the surrounding cells. In the method of WO 01/51087, the photosensitizing compound is conjugated to, for example, antibodies and antibody fragments that are capable of targeting the complex by binding to the endothelium that lines the neovascular tissue. Once bound to the endothelium in this way the conjugated photosensitizing compound may be activated to cause damage to the targeted endothelial cells.
The aim of PDT is very specific and its effects are narrow. Its aim is to kill target tissues to achieve the intended therapeutic effect, rather than to deliver a therapeutic agent whose beneficial effects might be achieved by diverse and/or multiple means (and not necessarily by toxicity to diseased tissue). A further disadvantage of PDT is that the reactive species produced upon activation of the photosensitizing compound tend to act indiscriminately on the surrounding (non-diseased) tissue. This form of therapy, therefore, may only be suitable for treating specific conditions, where damage to surrounding tissue can be tolerated and where destruction of a target tissue is the desired outcome. For other conditions, it may be preferable to deliver therapeutic drugs or agents to the target site whose effect is not necessarily to kill target tissues or cells. Rather, as well as being capable of destroying target tissues and cells, such agents might also be designed to inhibit a biochemical process (such as inflammation), to suppress infection (e.g. antibiotics and antiviral agents), to act as an agonist or antagonist of an endogenous agent (such as Vasoactive Endothelial Growth Factor (VEGF)), or to modulate an endogenous pathway in some other way.